Background: The prognosis of platinum-refractory ED-SCLC is poor, with ~95% of pts failing to respond to topotecan, the only approved 2^ndline treatment. SCLC is associated with a high mutation load and genomic instability, and data suggest that enhanced DNA repair could be a resistance mechanism. As such, immunotherapies and DNA damage repair inhibitors may be beneficial in this disease setting. Durvalumab (D) is a selective, high-affinity, engineered human IgG1 mAb that blocks PD-L1 binding to PD-1 and CD80. Tremelimumab (T) is a selective human IgG2 mAb against CTLA-4. In a Phase 1b study in NSCLC (NCT02000947), D + T showed encouraging activity and manageable tolerability. AZD1775 is a small-molecule inhibitor of the DNA damage checkpoint kinase WEE1 that potentiates genotoxic chemotherapies and is being developed for the treatment of advanced solid tumors with genetic deficiencies in DNA repair mechanisms. In a Phase 2 study in platinum-refractory p53 mutated ovarian cancer (NCT01164995), AZD1775 + carboplatin showed promising activity and an acceptable safety profile. Methods: BALTIC (NCT02937818) is a Phase 2, open-label, multicenter, multi-arm, exploratory, signal-searching study to assess the preliminary activity of novel treatment combinations in refractory ED-SCLC. Eligible pts will have progressed during, or within 90 days of completing 1^st line platinum-based chemotherapy, and have life expectancy ≥8 wks. Each arm is independent and will open sequentially to enroll up to 20 pts. The study will open initially with 2 arms: D 1500 mg + T 75 mg i.v. q4w for 4 doses, followed by D monotherapy 1500 mg i.v. q4w (Arm A); and oral AZD1775 225 mg bid for 2.5 days from Day 1 + carboplatin AUC 5 on Day 1 i.v. q3w (Arm B). Pts will receive treatment until confirmed disease progression or discontinuation. Further arms may be added to assess other combinations once safe and tolerable doses and schedules have been established. The primary endpoint is investigator-assessed ORR (RECIST v1.1). Secondary endpoints include duration of response, disease control rate, time to response, PFS, OS, PK, safety and tolerability. Recruitment is ongoing. Clinical trial information: NCT02937818